miRNA profile of luminal breast cancer subtyptes in Slovak women.

OBJECTIVE: Aberrant expression of short, non-coding RNA molecules (miRNA) leads to breast cancer initiation, progression and metastasing. The miRNA expression level associates with imunohistochemical profile, histopathological parameters, clinical outcomes, prognoses and therapeutical response. The aim of this study was to analyse the whole spectrum of miRNA by microarray method and to define relevant miRNAs describing biological characteristics of luminal breast cancer subtypes. DESIGN: Cross-sectional study, basic research. SETTING: Biomedical center Martin, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovakia. METHODS: We analysed 16 tissue samples of Luminal A/B breast cancer types and 16 breast tissue samples without pathological findings. The microarray technology by Agilent was used to analyse 2549 miRNAs by SurePrint G3 Human miRNA kit v.21. The results were assessed by AgiMicroRNA Bioconductor library within Limma pack. RESULTS: The analyses of the lowest FDR p-value and the highest logFC value selected the oncomiR miR-182 as the most dominant with higher expression in cancer tissues than in normal tissues, followed by miR-21, miR342-3p/5p and miR-6826. The miR-4324 and cluster of miR-99a/let7c/miR-125b dominated in the group of miRNAs with lower expression in cancer tissues compared to normal tissues. CONCLUSION: The first results of this study complement biological characteristics of luminal breast cancer subptypes, represent basis for follow-up projects focused on the clarification of relevant signaling pathways and promise new and innovative breast cancer treatment based on the precise, tailored therapy by targeting specific miRNAs involved in the most important carcinogenesis mechanisms.

Factors affecting the uterine sarcomas developement and possibilities of their clinical diagnosis.

OBJECTIVE: The main goal of this article is to summarize the known factors underlying the tumorigenesis of sarcomas and to present the limitations of clinical diagnosis. DESIGN: A review article. SETTINGS: Division of Molecular Medicine, Biomedical Center, JLF UK Martin, Slovakia; Department of Gynaecology and Obstetrics JLF UK and UNM Martin, Slovakia; Division of Oncology, Biomedical Center in Martin, JLF UK, Martin, Slovakia. METHODS: An analysis and summarisation of published studies about etiology, aberrant factors and limmitations of clinical diagnosis of uterne sarcomas. RESULTS AND CONCLUSIONS: Uterine sarcomas are heterogenous, malignant tumour types of mesenchymal origin with a very low incidence. On the other hand, sarcomas are very aggressive tumours with a poor prognosis, and a very low chance of surviving in general. The most common types of sarcomas are leiomyosarcomas, followed in percentage occurrence by endometrial stromal sarcomas and adenosarcomas. This tumour pathogenesis remains still relatively unknown. There are recognized only several predisposition factor types, and the limitated molecular-genetic aberrations associated with their occurrence. Importantly, the potential perturbation of the malignant mass during the implementation of invasive methods can be considered as the most serious risk factor. In regards to the visualization methods application, there are still limited ways of distinguishing between malignant and benign forms, especially in the case of leiomyosarcomas.

Potential of survivin for treatment of gynaecological tumour diseases.

OBJECTIVE: The main purpose of this article is to consolidate known facts about survivin, its contribution to inhibition of apoptosis, impact to tumorigenesis of gynaecological types of tumours. and possibilities of inhibition of survivin on molecular-genetic levels. DESIGN: A review article. SETTINGS: Division of Molecular Medicine, Biomedical Center in Martin, JLF UK Martin, Slovakia; Department of Gynaecology and Obstetrics JLF UK and UNM Martin, Slovakia; Division of Oncology, Biomedical Center, JLF UK Martin, Slovakia. METHODS: An analysis of the literature using database search engines focused on aberations in fuction of survivin, primarily in case of gynaecological tumours and possibilities of its inhibition. RESULTS AND CONCLUSIONS: Survivin is the smallest member of inhibitor of apoptosis (IAP) family. Despite of its size and affiliation to mentioned gene family, survivin can affect besides inhibition of apoptosis also proper process of mitosis, DNA reparation and angiogenesis. High levels of survivin expression are typical for fetal tissues during intrauterine developement. In healthy, adult tissues remain levels of survivin very low. Nonetheless, abundant expression of survivin is in many cases typical for various types of cancer, including gynaecologycal cancers Generally, it is possible to associate higher amounts of survivin with poor prognosis and resistance to chemo- or radiotherapy.

[Leiomyomas of the uterine body: Molecular-genetical aspects of formation and development]. / Leiomyómy tela maternice: Molekulárno-genetické aspekty vzniku a rozvoja.

OBJECTIVE: An overview of the molecular-genetical aspects of formation and development of leiomyomas of the uterine body. DESIGN: A review article. SETTING: Department of Gynecology and Obstetrics, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Slovak Republic. METHODS: An analysis of the literature using database search engines PubMed, Blast, Science direct and Web of Knowledge focused on tumorigenesis of leiomyoma. RESULTS: Benign uterine leiomyomas, also known as myoma, fibroids or fibromyomas are the most common tumours located in the pelvic area of women. The prevalence of this disease reaches, on the global scale, values higher than 50%, depending on the ethnicity even up to 80% of women of reproductive age. Despite such a high value, the origin of leiomyomas is still unknown. The main reason is the heterogeneity of the disease, and a number of factors that influence their development. In the case of leiomyomata occurrence, it has so far been observed several genome rearrangements and a number of aberrantly expressed genes. There are several reasons for overexpression or underexpression of a particular gene, from a point mutation in the exon region of the gene, promoter or other regulatory sequences to epigenetic modifications, most commonly the nature of methylation, or more precisely inadequate regulation short molecule miRNA. Many of these genes belong to the group of tumour-suppressor genes, or more precisely to genes, which can affect the cell cycle in a different way and thus can affect even the cell division. The aim of this work is to describe the various factors influencing the formation of leiomyomas and their impact on tumorigenesis.

Telomerase and the process of cervical carcinogenesis.

The integration of HPV infection in the epithelial cells is a key step in the induction of malignant changes of cervical cancer. In addition, there appear also other genomic alterations. Multi-step nature of carcinogenesis includes sequential accumulation of genetic changes that lead to invasive growth and progression. It is therefore necessary to understand the cervical carcinogenesis accompanied by chromosomal aberrations. The most common aberrations contain regions 5p15 and 3q26 coding the enzyme telomerase. For cervical cancer, telomerase is already active in case of precancerous lesions. Amplification of chromosomal region 3q26 detected by fluorescence in situ hybridization has the highest combined sensitivity and specificity in distinguishing low-grade lesion of high-grade lesions or invasive disease compared to the liquid-based cytology (LBC) and HPV DNA.

Malignant tumors of the uterine corpus: molecular background of their origin.

Tumors of the uterine corpus can be divided into two main groups: endometrial tumors and mesenchymal tumors. The former ones are common gynecological diseases, whereas malignant mesenchymal tumors, which behave in a much more aggressive way, are quite rare with a poorer prognosis. The most common type of endometrial tumors is endometrioid adenocarcinomas, and in case of mesenchymal tumors, these are carcinosarcomas, or leiomyosarcomas, if only clear types of tumors are taken into account. The objective of this article is to review molecular-genetic abnormalities associated with tumorigenesis of both types of tumors, with focus on the most aggressive forms. This view includes a different expression pattern of genes, usually aberrant in cases of uterine cancer that can arise due to epigenetic modifications, mostly hypermethylation of promoters or microRNA (miRNA)'s interference with concrete genes. Furthermore, clinical predispositions of tumorigenesis, involving hormonal factors, age, and ethnicity, are also mentioned.